Architecture of the Mediator head module

Tsuyoshi Imasaki, Guillermo Calero, Gang Cai, Kuang Lei Tsai, Kentaro Yamada, Francesco Cardelli, Hediye Erdjument-Bromage, Paul Tempst, Imre Berger, Guy Lorch Kornberg, Francisco J. Asturias, Roger D. Kornberg, Yuichiro Takagi

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Mediator is a key regulator of eukaryotic transcription, connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II (Pol II). In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a total mass of more than one megadalton (refs 5, 6) and is organized into three modules, called head, middle/arm and tail. Our understanding of Mediator assembly and its role in regulating transcription has been impeded so far by limited structural information. Here we report the crystal structure of the essential Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a resolution of 4.3 à ¥ngstrà ¶ms. Our structure reveals three distinct domains, with the integrity of the complex centred on a bundle of ten helices from five different head subunits. An intricate pattern of interactions within this helical bundle ensures the stable assembly of the head subunits and provides the binding sites for general transcription factors and Pol II. Our structural and functional data suggest that the head module juxtaposes transcription factor IIH and the carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal architectural principles underlying the role of Mediator in the regulation of gene expression.

Original languageEnglish (US)
Pages (from-to)240-243
Number of pages4
JournalNature
Volume475
Issue number7355
DOIs
StatePublished - Jul 14 2011

Fingerprint

Head
Transcription Factor TFIIH
General Transcription Factors
RNA Polymerase II
Gene Expression Regulation
Saccharomyces cerevisiae
Arm
Yeasts
Binding Sites
Phosphorylation
DNA

ASJC Scopus subject areas

  • General

Cite this

Imasaki, T., Calero, G., Cai, G., Tsai, K. L., Yamada, K., Cardelli, F., ... Takagi, Y. (2011). Architecture of the Mediator head module. Nature, 475(7355), 240-243. https://doi.org/10.1038/nature10162

Architecture of the Mediator head module. / Imasaki, Tsuyoshi; Calero, Guillermo; Cai, Gang; Tsai, Kuang Lei; Yamada, Kentaro; Cardelli, Francesco; Erdjument-Bromage, Hediye; Tempst, Paul; Berger, Imre; Kornberg, Guy Lorch; Asturias, Francisco J.; Kornberg, Roger D.; Takagi, Yuichiro.

In: Nature, Vol. 475, No. 7355, 14.07.2011, p. 240-243.

Research output: Contribution to journalArticle

Imasaki, T, Calero, G, Cai, G, Tsai, KL, Yamada, K, Cardelli, F, Erdjument-Bromage, H, Tempst, P, Berger, I, Kornberg, GL, Asturias, FJ, Kornberg, RD & Takagi, Y 2011, 'Architecture of the Mediator head module', Nature, vol. 475, no. 7355, pp. 240-243. https://doi.org/10.1038/nature10162
Imasaki T, Calero G, Cai G, Tsai KL, Yamada K, Cardelli F et al. Architecture of the Mediator head module. Nature. 2011 Jul 14;475(7355):240-243. https://doi.org/10.1038/nature10162
Imasaki, Tsuyoshi ; Calero, Guillermo ; Cai, Gang ; Tsai, Kuang Lei ; Yamada, Kentaro ; Cardelli, Francesco ; Erdjument-Bromage, Hediye ; Tempst, Paul ; Berger, Imre ; Kornberg, Guy Lorch ; Asturias, Francisco J. ; Kornberg, Roger D. ; Takagi, Yuichiro. / Architecture of the Mediator head module. In: Nature. 2011 ; Vol. 475, No. 7355. pp. 240-243.
@article{b272a4e7ff8f476981ea39cd53f5961d,
title = "Architecture of the Mediator head module",
abstract = "Mediator is a key regulator of eukaryotic transcription, connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II (Pol II). In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a total mass of more than one megadalton (refs 5, 6) and is organized into three modules, called head, middle/arm and tail. Our understanding of Mediator assembly and its role in regulating transcription has been impeded so far by limited structural information. Here we report the crystal structure of the essential Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a resolution of 4.3 {\~A} ¥ngstr{\~A} ¶ms. Our structure reveals three distinct domains, with the integrity of the complex centred on a bundle of ten helices from five different head subunits. An intricate pattern of interactions within this helical bundle ensures the stable assembly of the head subunits and provides the binding sites for general transcription factors and Pol II. Our structural and functional data suggest that the head module juxtaposes transcription factor IIH and the carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal architectural principles underlying the role of Mediator in the regulation of gene expression.",
author = "Tsuyoshi Imasaki and Guillermo Calero and Gang Cai and Tsai, {Kuang Lei} and Kentaro Yamada and Francesco Cardelli and Hediye Erdjument-Bromage and Paul Tempst and Imre Berger and Kornberg, {Guy Lorch} and Asturias, {Francisco J.} and Kornberg, {Roger D.} and Yuichiro Takagi",
year = "2011",
month = "7",
day = "14",
doi = "10.1038/nature10162",
language = "English (US)",
volume = "475",
pages = "240--243",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7355",

}

TY - JOUR

T1 - Architecture of the Mediator head module

AU - Imasaki, Tsuyoshi

AU - Calero, Guillermo

AU - Cai, Gang

AU - Tsai, Kuang Lei

AU - Yamada, Kentaro

AU - Cardelli, Francesco

AU - Erdjument-Bromage, Hediye

AU - Tempst, Paul

AU - Berger, Imre

AU - Kornberg, Guy Lorch

AU - Asturias, Francisco J.

AU - Kornberg, Roger D.

AU - Takagi, Yuichiro

PY - 2011/7/14

Y1 - 2011/7/14

N2 - Mediator is a key regulator of eukaryotic transcription, connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II (Pol II). In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a total mass of more than one megadalton (refs 5, 6) and is organized into three modules, called head, middle/arm and tail. Our understanding of Mediator assembly and its role in regulating transcription has been impeded so far by limited structural information. Here we report the crystal structure of the essential Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a resolution of 4.3 à ¥ngstrà ¶ms. Our structure reveals three distinct domains, with the integrity of the complex centred on a bundle of ten helices from five different head subunits. An intricate pattern of interactions within this helical bundle ensures the stable assembly of the head subunits and provides the binding sites for general transcription factors and Pol II. Our structural and functional data suggest that the head module juxtaposes transcription factor IIH and the carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal architectural principles underlying the role of Mediator in the regulation of gene expression.

AB - Mediator is a key regulator of eukaryotic transcription, connecting activators and repressors bound to regulatory DNA elements with RNA polymerase II (Pol II). In the yeast Saccharomyces cerevisiae, Mediator comprises 25 subunits with a total mass of more than one megadalton (refs 5, 6) and is organized into three modules, called head, middle/arm and tail. Our understanding of Mediator assembly and its role in regulating transcription has been impeded so far by limited structural information. Here we report the crystal structure of the essential Mediator head module (seven subunits, with a mass of 223 kilodaltons) at a resolution of 4.3 à ¥ngstrà ¶ms. Our structure reveals three distinct domains, with the integrity of the complex centred on a bundle of ten helices from five different head subunits. An intricate pattern of interactions within this helical bundle ensures the stable assembly of the head subunits and provides the binding sites for general transcription factors and Pol II. Our structural and functional data suggest that the head module juxtaposes transcription factor IIH and the carboxy-terminal domain of the largest subunit of Pol II, thereby facilitating phosphorylation of the carboxy-terminal domain of Pol II. Our results reveal architectural principles underlying the role of Mediator in the regulation of gene expression.

UR - http://www.scopus.com/inward/record.url?scp=79960434142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960434142&partnerID=8YFLogxK

U2 - 10.1038/nature10162

DO - 10.1038/nature10162

M3 - Article

C2 - 21725323

AN - SCOPUS:79960434142

VL - 475

SP - 240

EP - 243

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7355

ER -